ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2011A>T (p.Asn671Tyr)

dbSNP: rs63751232
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002417363 SCV002722948 likely pathogenic Hereditary cancer-predisposing syndrome 2021-09-10 criteria provided, single submitter clinical testing The p.N671Y variant (also known as c.2011A>T), located in coding exon 13 of the MSH2 gene, results from an A to T substitution at nucleotide position 2011. The asparagine at codon 671 is replaced by tyrosine, an amino acid with dissimilar properties. This variant has been identified in patients with clinical histories consistent with Lynch syndrome (Ambry internal data; Salehi M et al. J. Sci. I. R. I. 2009 20;1: 7-12; Sharp A et al. Hum. Mutat. 2004 Sep;24:272; Tournier I et al. Hum. Mutat. 2008 Dec;29:1412-24). A methylation tolerance-based functional assay in a MSH2-deficient human colorectal cell line indirectly demonstrated cells with this alteration to have reduced MMR activity (Bouvet D et al. Gastroenterology. 2019 08;157:421-431). In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was determined to be functionally deleterious (Jia X et al. Am J Hum Genet, 2021 01;108:163-175). This alteration is part of the Walker Loop and located within the Walker A motif, which is believed to be involved in protein function; therefore, this alteration is predicted to be structurally disruptive (Warren JJ et al. Mol. Cell. 2007 May;26:579-92; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Myriad Genetics, Inc. RCV003454316 SCV004186597 likely pathogenic Lynch syndrome 1 2023-08-07 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 30998989]. This variant is expected to disrupt protein structure [Myriad internal data].

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.